Physical Fitness Linked to Larger Hippocampus in Elderly

Regular exercise might bulk up more than your muscles. According to a recent study, a memory-related brain region known as the hippocampus is larger in elderly people who have greater aerobic fitness.

“This brain region has a lot of clinical significance because it’s impacted in Alzheimer’s disease and dementia in general,” says Kirk Erickson, who was first author on the study while a postdoctoral fellow at the University of Illinois, Urbana-Champaign.

Evidence that exercise improves brain function in the elderly, or at least slows the brain’s decline, has been building up for the past few years. Studies of large elderly populations have linked a sedentary lifestyle to greater risk of age-related cognitive impairment. Animal and human studies also have shown that aerobic exercise, and associated improvements in breathing and blood circulation, leads to improvements in some cognitive skills and even increases in whole-brain volume. Studies in rodents have found that the hippocampus, which in humans seems particularly sensitive to age-related shrinkage, can be enlarged by exercise.

“What we didn’t know was whether the same is true for humans,” says Art Kramer, principal investigator for the study and head of a large laboratory at the University of Illinois’ Beckman Institute for Advanced Science and Technology.

After recruiting 165 adults ages 59 to 81, Erickson, Kramer and their colleagues measured the subjects’ aerobic fitness on a treadmill test; gauged their hippocampal volume with high-resolution structural magnetic resonance imaging; and determined their proficiency in spatial memory—which is known to be hippocampus-dependent—on a standard test.

They found that aerobic fitness levels in the subjects correlated strongly with hippocampal volume, for both the right and left hippocampus and even after controlling for the ordinary variations in hippocampal volume that are known to occur according to age, sex and years of education.

In the study, aerobic fitness also correlated with spatial-memory proficiency, and statistical analyses suggested that this cognitive improvement was linked to the increase in hippocampal volume.

Following up: an intervention study

Though the current study shows that aerobic fitness levels in the 165 subjects were positively associated with hippocampal volume and spatial memory performance, because of its design it does not show if those fitness levels were the cause of the increases in hippocampal volume.

However, a follow-on “intervention trial,” now under way with about 120 of the same patients, is designed to show whether thrice-weekly aerobic exercise in the elderly improves hippocampal volume and other cognition-related measures.

“We should have some results from that within the next six to eight months,” says Erickson, now an assistant professor of psychology at the University of Pittsburgh. “If they turn out the way we expect, those results should be quite provocative.”

How exercise builds brains

It isn’t clear why the human hippocampus would become larger with aerobic exercise. But Mark Mattson, a researcher at the National Institute on Aging in Baltimore, heads a team that has studied this question with animal experiments.

“If you give mice or rats access to running wheels, they’ll run anywhere from 3 to 7 miles every day,” he says. Hippocampal tissue from these super-fit animals shows a proliferation of blood vessels and an increase in the growth of dendrites, the input stalks of neurons. Perhaps most important, this tissue also shows increased production of new neurons from stem cells, a process called neurogenesis that is known to occur in the hippocampus in adult humans. “All of those would together increase the size of the hippocampus,” Mattson says.

These processes appear to be driven by several nerve-cell and vascular growth factors that Mattson’s lab and others have been studying for their therapeutic potential. But unless and until those efforts pay off with drug development, the best way to deliver those growth factors to the hippocampus may be the old-fashioned way: through exercise.